AMERICAN THORACIC SOCIETY DOCUMENTS - GDPharmD

AMERICAN THORACIC SOCIETY

DOCUMENTS

Diagnosis and Treatment of Adults with Community-acquired

Pneumonia

An Of?cial Clinical Practice Guideline of the American Thoracic Society and

Infectious Diseases Society of America

Joshua P. Metlay*, Grant W. Waterer*, Ann C. Long, Antonio Anzueto, Jan Brozek, Kristina Crothers, Laura A. Cooley,

Nathan C. Dean, Michael J. Fine, Scott A. Flanders, Marie R. Grif?n, Mark L. Metersky, Daniel M. Musher,

Marcos I. Restrepo, and Cynthia G. Whitney; on behalf of the American Thoracic Society and Infectious Diseases

Society of America

THIS OFFICIAL CLINICAL PRACTICE GUIDELINE WAS APPROVED BY THE AMERICAN THORACIC SOCIETY MAY 2019 AND THE INFECTIOUS DISEASES SOCIETY OF AMERICA

AUGUST 2019

Background: This document provides evidence-based clinical

practice guidelines on the management of adult patients with

community-acquired pneumonia.

Methods: A multidisciplinary panel conducted pragmatic

systematic reviews of the relevant research and applied Grading of

Recommendations, Assessment, Development, and Evaluation

methodology for clinical recommendations.

Results: The panel addressed 16 speci?c areas for recommendations

spanning questions of diagnostic testing, determination of site of

care, selection of initial empiric antibiotic therapy, and subsequent

Contents

Overview

Introduction

Methods

Recommendations

management decisions. Although some recommendations remain

unchanged from the 2007 guideline, the availability of results from

new therapeutic trials and epidemiological investigations led to

revised recommendations for empiric treatment strategies and

additional management decisions.

Conclusions: The panel formulated and provided the rationale for

recommendations on selected diagnostic and treatment strategies

for adult patients with community-acquired pneumonia.

Keywords: community-acquired pneumonia; pneumonia; patient

management

Question 1: In Adults with CAP,

Should Gram Stain and Culture

of Lower Respiratory Secretions

Be Obtained at the Time of

Diagnosis?

Question 2: In Adults with CAP,

Should Blood Cultures Be

Obtained at the Time of Diagnosis?

Question 3: In Adults with CAP,

Should Legionella and

*Co¨Cfirst authors.

Endorsed by the Society of Infectious Disease Pharmacists July 2019.

ORCID IDs: 0000-0003-2259-6282 (J.P.M.); 0000-0002-7222-8018 (G.W.W.); 0000-0002-7007-588X (A.A.); 0000-0002-3122-0773 (J.B.);

0000-0001-9702-0371 (K.C.); 0000-0002-5127-3442 (L.A.C.); 0000-0002-1996-0533 (N.C.D.); 0000-0003-3470-9846 (M.J.F.);

0000-0002-8634-4909 (S.A.F.); 0000-0001-7114-7614 (M.R.G.); 0000-0003-1968-1400 (M.L.M.); 0000-0002-7571-066X (D.M.M.);

0000-0001-9107-3405 (M.I.R.); 0000-0002-1056-3216 (C.G.W.).

Supported by the American Thoracic Society and Infectious Diseases Society of America.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. CDC.

An Executive Summary of this document is available at .

You may print one copy of this document at no charge. However, if you require more than one copy, you must place a reprint order. Domestic reprint orders:

amy.schriver@; international reprint orders: louisa.mott@.

This article has an online supplement, which is accessible from this issue¡¯s table of contents at .

Am J Respir Crit Care Med Vol 200, Iss 7, pp e45¨Ce67, Oct 1, 2019

Copyright ? 2019 by the American Thoracic Society

DOI: 10.1164/rccm.201908-1581ST

Internet address:

American Thoracic Society Documents

e45

AMERICAN THORACIC SOCIETY DOCUMENTS

Pneumococcal Urinary Antigen

Testing Be Performed at the

Time of Diagnosis?

Question 4: In Adults with CAP,

Should a Respiratory Sample Be

Tested for In?uenza Virus at the

Time of Diagnosis?

Question 5: In Adults with CAP,

Should Serum Procalcitonin plus

Clinical Judgment versus

Clinical Judgment Alone Be

Used to Withhold Initiation of

Antibiotic Treatment?

Question 6: Should a Clinical

Prediction Rule for Prognosis

plus Clinical Judgment versus

Clinical Judgment Alone Be

Used to Determine Inpatient

versus Outpatient Treatment

Location for Adults with CAP?

Question 7: Should a Clinical

Prediction Rule for Prognosis

plus Clinical Judgment versus

Clinical Judgment Alone Be

Used to Determine Inpatient

General Medical versus Higher

Overview

In the more than 10 years since the last

American Thoracic Society(ATS)/Infectious

Diseases Society of America (IDSA)

community-acquired pneumonia (CAP)

guideline (1), there have been changes in

the process for guideline development, as

well as generation of new clinical data. ATS

and IDSA agreed on moving from the

narrative style of previous documents to the

Grading of Recommendations Assessment,

Development, and Evaluation (GRADE)

format. We thus developed this updated

CAP guideline as a series of questions

answered from available evidence in an ¡°is

option A better than option B¡± format

using the Patient or Population,

Intervention, Comparison, Outcome

(PICO) framework (2).

Given the expansion in information

related to the diagnostic, therapeutic, and

management decisions for the care of

patients with CAP, we have purposely

narrowed the scope of this guideline to

address decisions from the time of clinical

diagnosis of pneumonia (i.e., signs and

symptoms of pneumonia with radiographic

con?rmation) to completion of

antimicrobial therapy and follow-up chest

e46

Levels of Inpatient Treatment

Intensity (ICU, Step-Down, or

Telemetry Unit) for Adults with

CAP?

Question 8: In the Outpatient

Setting, Which Antibiotics Are

Recommended for Empiric

Treatment of CAP in Adults?

Question 9: In the Inpatient

Setting, Which Antibiotic

Regimens Are Recommended

for Empiric Treatment of

CAP in Adults without Risk

Factors for MRSA and

P. aeruginosa?

Question 10: In the Inpatient

Setting, Should Patients

with Suspected Aspiration

Pneumonia Receive Additional

Anaerobic Coverage beyond

Standard Empiric Treatment for

CAP?

Question 11: In the Inpatient

Setting, Should Adults with CAP

and Risk Factors for MRSA or

P. aeruginosa Be Treated with

imaging. The document does not address

either the initial clinical diagnostic criteria

or prevention of pneumonia.

CAP is an extraordinarily

heterogeneous illness, both in the range

of responsible pathogens and the host

response. Thus, the PICO questions we

identi?ed for this guideline do not represent

the full range of relevant questions about the

management of CAP but encompass a set of

core questions identi?ed as high priority by

the panel. In addition, although each

question was addressed using systematic

reviews of available high-quality studies,

the evidence base was often insuf?cient,

emphasizing the continued importance of

clinical judgment and experience in treating

patients with this illness and the need for

continued research.

Introduction

This guideline addresses the clinical entity of

pneumonia that is acquired outside of the

hospital setting. Although we recognize that

CAP is frequently diagnosed without the use

of a chest radiograph, especially in the

ambulatory setting, we have focused on

studies that used radiographic criteria for

Extended-Spectrum Antibiotic

Therapy Instead of Standard

CAP Regimens?

Question 12: In the Inpatient

Setting, Should Adults

with CAP Be Treated with

Corticosteroids?

Question 13: In Adults with CAP

Who Test Positive for In?uenza,

Should the Treatment Regimen

Include Antiviral Therapy?

Question 14: In Adults with

CAP Who Test Positive for

In?uenza, Should the Treatment

Regimen Include Antibacterial

Therapy?

Question 15: In Outpatient and

Inpatient Adults with CAP Who

Are Improving, What Is the

Appropriate Duration of

Antibiotic Treatment?

Question 16: In Adults with CAP

Who Are Improving, Should

Follow-up Chest Imaging Be

Obtained?

Conclusions

de?ning CAP, given the known inaccuracy

of clinical signs and symptoms alone for

CAP diagnosis (3). This guideline focuses

on patients in the United States who have

not recently completed foreign travel,

especially to regions with emerging

respiratory pathogens. This guideline also

focuses on adults who do not have an

immunocompromising condition, such as

inherited or acquired immune de?ciency or

drug-induced neutropenia, including

patients actively receiving cancer

chemotherapy, patients infected with HIV

with suppressed CD4 counts, and solid

organ or bone marrow transplant

recipients.

Antibiotic recommendations for the

empiric treatment of CAP are based on

selecting agents effective against the major

treatable bacterial causes of CAP.

Traditionally, these bacterial pathogens

include Streptococcus pneumoniae,

Haemophilus in?uenzae, Mycoplasma

pneumoniae, Staphylococcus aureus,

Legionella species, Chlamydia pneumoniae,

and Moraxella catarrhalis. The microbial

etiology of CAP is changing, particularly

with the widespread introduction of the

pneumococcal conjugate vaccine, and there

is increased recognition of the role of viral

American Journal of Respiratory and Critical Care Medicine Volume 200 Number 7 | October 1 2019

AMERICAN THORACIC SOCIETY DOCUMENTS

pathogens. The online supplement contains

a more detailed discussion of CAP

microbiology. As bacterial pathogens often

coexist with viruses and there is no current

diagnostic test accurate enough or fast

enough to determine that CAP is due solely

to a virus at the time of presentation (see

below), our recommendations are to

initially treat empirically for possible

bacterial infection or coinfection. In

addition, the emergence of multidrugresistant pathogens, including methicillinresistant S. aureus (MRSA) and

Pseudomonas aeruginosa, requires separate

recommendations when the risk of

each of these pathogens is elevated. We

acknowledge that other multidrug-resistant

Enterobacteriaceae can cause CAP,

including organisms producing extendedspectrum b-lactamase, but we do not

discuss them separately because they are

much less common and are effectively

covered by the strategies presented for

P. aeruginosa. Therefore, throughout this

document when discussing P. aeruginosa

we are also referring to other similar

multiresistant gram-negative bacteria.

We have maintained the convention

of separate recommendations on the

basis of the severity of illness. Although

historically site of care (outpatient,

inpatient general ward, or ICU) has served

as a severity surrogate, decisions about site

of care may be based on considerations

other than severity and can vary widely

between hospitals and practice sites.

We have therefore chosen to use the

IDSA/ATS CAP severity criteria that have

been validated and de?ne severe CAP as

present in patients with either one major

criterion or three or more minor criteria.

(Table 1)

This guideline reaf?rms many

recommendations from the 2007 statement.

However, new evidence and a new process

have led to signi?cant changes, which are

summarized in Table 2.

Methods

The guideline development methodology

and how con?ict of interest was managed

are presented in the online supplement. In

brief, the list of PICO questions was ?nalized

based on a prioritization of the most

important management decisions balanced

against the decision to reduce the overall

length of the document and total number of

American Thoracic Society Documents

recommendations to maximize readability

and usability. We followed the GRADE

standards for evaluating the evidence for

each PICO and assigned a quality of

evidence rating of high, moderate, low, or

very low. On the basis of the quality of

evidence, recommendations were assigned

as strong or conditional. In some cases,

strong recommendations were made in the

setting of low or very low quality of evidence

in accordance with the GRADE rules for

when such recommendations are allowable

(e.g., when the consequences of the

recommendation were high, such as

preventing harm or saving life). In all other

cases, recommendations that were based on

low or very low quality of evidence and not

believed to represent standards of care were

labeled as conditional recommendations.

Statements in favor of strong

recommendations begin with the words

¡°We recommend . . .¡±; statements in favor

of conditional recommendations begin

with the words ¡°We suggest . . . .¡±

Although we speci?ed pairwise PICO

questions for all antibiotic options in the

outpatient and inpatient settings, we

summarized the recommendations using

lists of treatment options, in no preferred

order, rather than retain the PICO format

for this section.

Recommendations

Question 1: In Adults with CAP,

Should Gram Stain and Culture of

Lower Respiratory Secretions Be

Obtained at the Time of Diagnosis?

Recommendation. We recommend not

obtaining sputum Gram stain and culture

routinely in adults with CAP managed in the

outpatient setting (strong recommendation,

very low quality of evidence).

We recommend obtaining pretreatment

Gram stain and culture of respiratory

secretions in adults with CAP managed in

the hospital setting who:

1. are classi?ed as severe CAP (see Table 1),

especially if they are intubated (strong

recommendation, very low quality of

evidence); or

2.

a. are being empirically treated for

MRSA or P. aeruginosa (strong

recommendation, very low quality

of evidence); or

b. were previously infected with MRSA

or P. aeruginosa, especially those

with prior respiratory tract infection

(conditional recommendation, very

low quality of evidence); or

c. were hospitalized and received

parenteral antibiotics, whether during the

hospitalization event or not, in the last

90 days (conditional recommendation,

very low quality of evidence).

Summary of the evidence. Arguments

for trying to determine the etiology of CAP

are that 1) a resistant pathogen may be

identi?ed; 2) therapy may be narrowed; 3)

some pathogens, such as Legionella, have

public health implications; 4) therapy may

be adjusted when patients fail initial

therapy; and 5) the constantly changing

epidemiology of CAP requires ongoing

evaluation.

These arguments stand in contrast to

the lack of high-quality evidence

demonstrating that routine diagnostic

testing improves individual patient

outcomes. Studies that speci?cally evaluated

the use of sputum Gram stain and culture

alone (4¨C7), or in combination with other

microbiological testing (8¨C11), also did not

demonstrate better patient outcomes.

The overall poor yield of sputum

evaluation for detecting organisms causing

CAP limits its impact on management and

patient outcomes. Obtaining a valid sputum

specimen can be challenging because of

patient-related characteristics (12¨C17).

Performance characteristics of testing also

vary by organism, receipt of prior

antibiotics, and setting. For example, in

patients with bacteremic pneumococcal

pneumonia who have not received

antibiotics, microscopic examination and

culture of a good-quality sputum sample

detects pneumococci in 86% of cases (18).

Rationale for the recommendation. In

balancing the lack of evidence supporting

routine sputum culture with the desire for

improved antimicrobial stewardship, the

committee voted to continue the stance of

previous guidelines in recommending

neither for nor against routinely obtaining

sputum Gram stain and culture in all adults

with CAP managed in the hospital setting.

Whether to culture patients or not should be

determined by individual clinicians on the

basis of clinical presentation, local

etiological considerations, and local

antimicrobial stewardship processes.

The committee identi?ed two

situations in which we recommend sputum

e47

AMERICAN THORACIC SOCIETY DOCUMENTS

Table 1. 2007 Infectious Diseases

Society of America/American Thoracic

Society Criteria for De?ning Severe

Community-acquired Pneumonia

Validated de?nition includes either one

major criterion or three or more

minor criteria

Minor criteria

Respiratory rate > 30 breaths/min

PaO2/FIO2 ratio < 250

Multilobar in?ltrates

Confusion/disorientation

Uremia (blood urea nitrogen

level > 20 mg/dl)

Leukopenia* (white blood cell

count , 4,000 cells/ml)

Thrombocytopenia (platelet

count , 100,000/ml)

Hypothermia (core temperature , 368 C)

Hypotension requiring aggressive ?uid

resuscitation

Major criteria

Septic shock with need for

vasopressors

Respiratory failure requiring mechanical

ventilation

*Due to infection alone (i.e., not chemotherapy

induced).

Gram stain and culture: in hospitalized

patients with severe CAP, and when strong

risk factors for MRSA and P. aeruginosa are

identi?ed, unless local etiological data have

already shown these pathogens are very

infrequently identi?ed in patients with CAP.

Patients who have severe CAP requiring

intubation should have lower respiratory tract

samples, such as endotracheal aspirates, sent

for Gram stain and culture promptly after

intubation, particularly as these patients may

be more likely to have pneumonia due to

MRSA or P. aeruginosa, and endotracheal

aspirates have a better yield of microbiological

organisms than sputum culture (19).

We recommend obtaining sputum for

Gram stain and culture in situations when

risk factors for MRSA or P. aeruginosa are

present, both when initial empiric therapy

is expanded to cover these pathogens and

when it is not expanded. In the former case,

negative microbiological test results may be

used to deescalate therapy, and in the latter

case, positive microbiological test results

may be used to adjust therapy. As discussed

later, although there are numerous studies

identifying individual risk factors for MRSA

and P. aeruginosa, many of these

associations are weak and vary across sites.

e48

The most consistently strong risk factor to

consider is prior infection with either

MRSA or P. aeruginosa. In addition,

hospitalization and treatment with

parenteral antibiotics in the last 90 days is

associated with an increased risk of these

pathogens, and so we recommend

sputum culture in this situation. These

recommendations are not based on highgrade evidence but re?ect the committee¡¯s

desire to improve antibiotic use as well as

improve clinicians¡¯ understanding of their

local pathogen prevalences and resistance

patterns, which we believe are key to

selecting appropriate empiric antibiotic

therapy.

Research needed in this area. Rapid,

cost-effective, sensitive, and speci?c

diagnostic tests to identify organisms

causing CAP have potential to improve

routine care by supporting the use of

targeted therapy, especially when there

are risk factors for antibiotic-resistant

pathogens. All new diagnostic tests should

be assessed in high-quality research studies

that address the impact of testing strategies

on treatment decisions and patient

outcomes.

Question 2: In Adults with CAP,

Should Blood Cultures Be Obtained at

the Time of Diagnosis?

Recommendation. We recommend not

obtaining blood cultures in adults with CAP

managed in the outpatient setting (strong

recommendation, very low quality of

evidence).

We suggest not routinely obtaining blood

cultures in adults with CAP managed in the

hospital setting (conditional recommendation,

very low quality of evidence).

We recommend obtaining

pretreatment blood cultures in adults with

CAP managed in the hospital setting who:

1. are classi?ed as severe CAP (see Table 1)

(strong recommendation, very low

quality of evidence); or

2.

a. are being empirically treated for

MRSA or P. aeruginosa (strong

recommendation, very low quality of

evidence); or

b. were previously infected with MRSA

or P. aeruginosa, especially those

with prior respiratory tract infection

(conditional recommendation, very

low quality of evidence); or

c. were hospitalized and received

parenteral antibiotics, whether during

the hospitalization event or not,

in the last 90 days (conditional

recommendation, very low quality of

evidence).

Summary of the evidence. There are no

high-quality studies that speci?cally

compared patient outcomes with and

without blood culture testing. One large

observational study found lower mortality

for hospitalized patients associated with

obtaining blood cultures at the time of

admission (20). Three subsequent (smaller)

observational studies found similar

associations between in-hospital mortality

and having blood cultures within 24 hours

of admission, but the results were not

statistically signi?cant (8, 21, 22).

The yield of blood cultures in most

series of adults with nonsevere CAP is low,

ranging from 2% (outpatients) to 9%

(inpatients) (14, 21, 23, 24); furthermore,

blood cultures rarely result in an

appropriate change in empiric therapy (25),

and blood specimens that include skin

contaminants can generate false-positive

test results. Growth of organisms such as

coagulase-negative staphylococci, which are

not recognized as CAP pathogens (26), may

lead to inappropriate antimicrobial use that

increases the risk for adverse drug effects.

A study of adults hospitalized with CAP

found blood cultures were associated with

a signi?cant increase in length of stay and

duration of antibiotic therapy (27). Given the

observational nature of these studies, it is

unknown whether the associations found with

blood cultures and patient outcomes were

causal or due to unmeasured confounding

factors, including severity of illness.

Rationale for the recommendation.

Although additional diagnostic information

could improve the quality of treatment

decisions, support for routine collection of

blood cultures is reduced by the low quality of

studies demonstrating clinical bene?t. Routinely

obtaining blood cultures may generate falsepositive results that lead to unnecessary

antibiotic use and increased length of stay.

In severe CAP, delay in covering lesscommon pathogens can have serious

consequences. Therefore, the potential bene?t

of blood cultures is much larger when results

can be returned within 24 to 48 hours.

The rationale for the recommendation

for blood cultures in the setting of risk

factors for MRSA and P. aeruginosa is the

same as for sputum culture.

American Journal of Respiratory and Critical Care Medicine Volume 200 Number 7 | October 1 2019

AMERICAN THORACIC SOCIETY DOCUMENTS

Table 2. Differences between the 2019 and 2007 American Thoracic Society/Infectious Diseases Society of America

Community-acquired Pneumonia Guidelines

Recommendation

2007 ATS/IDSA Guideline

2019 ATS/IDSA Guideline

Sputum culture

Primarily recommended in patients with

severe disease

Now recommended in patients with severe

disease as well as in all inpatients

empirically treated for MRSA or

Pseudomonas aeruginosa

Blood culture

Primarily recommended in patients with

severe disease

Now recommended in patients with severe

disease as well as in all inpatients

empirically treated for MRSA or P.

aeruginosa

Macrolide monotherapy

Strong recommendation for outpatients

Conditional recommendation for outpatients

based on resistance levels

Use of procalcitonin

Not covered

Not recommended to determine need for

initial antibacterial therapy

Use of corticosteroids

Not covered

Recommended not to use. May be considered

in patients with refractory septic shock

Use of healthcare-associated pneumonia

category

Accepted as introduced in the 2005

ATS/IDSA hospital-acquired and

ventilator-associated pneumonia

guidelines

Recommend abandoning this categorization.

Emphasis on local epidemiology and

validated risk factors to determine need for

MRSA or P. aeruginosa coverage.

Increased emphasis on deescalation of

treatment if cultures are negative

Standard empiric therapy for severe CAP

b-Lactam/macrolide and

b-lactam/?uoroquinolone combinations

given equal weighting

Both accepted but stronger evidence in favor

of b-lactam/macrolide combination

Routine use of follow-up chest imaging

Not addressed

Recommended not to obtain. Patients may be

eligible for lung cancer screening, which

should be performed as clinically indicated

Definition of abbreviations: ATS = American Thoracic Society; CAP = community-acquired pneumonia; IDSA = Infectious Diseases Society of America;

MRSA = methicillin-resistant Staphylococcus aureus.

Question 3: In Adults with CAP,

Should Legionella and Pneumococcal

Urinary Antigen Testing Be Performed

at the Time of Diagnosis?

Recommendation. We suggest not

routinely testing urine for pneumococcal

antigen in adults with CAP (conditional

recommendation, low quality of

evidence), except in adults with severe

CAP (conditional recommendation, low

quality of evidence).

We suggest not routinely testing urine

for Legionella antigen in adults with CAP

(conditional recommendation, low quality

of evidence), except

1. in cases where indicated by

epidemiological factors, such as

association with a Legionella outbreak

or recent travel (conditional

recommendation, low quality of

evidence); or

American Thoracic Society Documents

2. in adults with severe CAP (see Table 1)

(conditional recommendation, low

quality of evidence).

We suggest testing for Legionella

urinary antigen and collecting lower

respiratory tract secretions for Legionella

culture on selective media or Legionella

nucleic acid ampli?cation testing in

adults with severe CAP (conditional

recommendation, low quality of evidence).

Summary of the evidence. Falguera and

colleagues (28) randomized 177 patients to

pathogen-directed treatment (targeted

treatment) on the basis of results of urinary

antigen testing for S. pneumoniae and

Legionella versus empirical guidelinedirected treatment. Of the 88 patients in the

targeted treatment arm, 25% had a positive

urinary antigen test and received pathogendirected therapy. There were no statistical

differences in death, clinical relapse, ICU

admission, length of hospitalization, or

length of antibiotic treatment (28). A

second trial of 262 patients included

a broader range of microbiological testing

(sputum and blood cultures) and only

Legionella urinary antigen testing, but

patients receiving pathogen-directed

therapy had similar clinical outcomes to

patients receiving empirical, guidelinedirected therapy, including mortality, rates

of clinical failure, and length of

hospitalization (10).

One observational study evaluated cost

and antibiotic selection in patients during

two time periods, with and without

pneumococcal urinary antigen testing, but

found no differences during the two

time periods (29). In contrast, other

observational studies that have evaluated

the impact of prior CAP guideline

concordance (including initial diagnostic

testing with urinary antigen tests and

blood cultures, along with site of care

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